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Chapter 16/Androgen Treatment of the Hypogonadal Male 317 FORMULATIONS AVAILABLE FOR T-REPLACEMENT THERAPY Testosterone formulations that are available in the United States for treatment of male hypogonadism include parenteral 17β-hydroxyl T esters and transdermal T patches or gel (see Table 1) (16). Although oral 17α-alkylated androgen preparations (e.g., methyltestosterone and fluoxymesterone) are available, they have low biopotency and bioavailability, and it is difficult to achieve full androgen replacement with these weak androgens (16). Also, they significantly lower high-density lipoprotein (HDL) and raise low-density lipoprotein (LDL) cholesterol, are expensive, and have the potential to cause hepatotoxicity (cholestasis, jaundice, peliosis hepatis, and benign and malignant hepatic tumors). Because oral 17α-alkylated androgens have fewer therapeutic benefits and are associated with potentially greater risks compared to T esters or transdermal T formulations, they should not be used for androgen-replacement therapy of hypogonadal men. Parenteral T Esters Prior to the availability of transdermal T formulations, the long-acting, clinically equivalent, parenteral 17β-hydroxyl T esters T enanthate (Delatestryl ® ; Bio-Technology General, Iselin, NJ) and cypionate (Dep-Testosterone ® , Pharmacia &Upjohn, Kalamazoo, MI) were the most effective, practical inexpensive, and safe preparations for androgen replacement in hypogonadal men (16,21,22). Although transdermal T formulations provide a more physiological T replacement and are effective and practical alternatives to T injections, 17β-hydroxyl T esters continue to be used for androgen-replacement therapy, primarily because they are the least expensive method of T treatment. Also, some subjects who have been treated both with parenteral and transdermal T prefer T ester injections. Hydrophobic 17β-hydroxyl T esters are formulated in an oil vehicle (sesame oil for T enanthate and cottonseed oil for T cypionate). Following intramuscular injection, T esters are released slowly and hydrolyzed rapidly to T following release, resulting in an extended duration of T release and action into the circulation. In adult hypogonadal men, the usual starting dose of T enanthate or cypionate is 150– 200 mg im every 2 wk. Following injection of 200 mg of a T ester, serum T levels increase to the upper normal range or above for a few days and then gradually decline over 2 wk to the lower normal range or sometimes below, prior to the next injection (see Fig. 1A) (21,22). This wide excursion of serum T levels between T ester injections may be associated with disturbing fluctuations in sexual desire and function, energy, and mood. In men who experience reduced libido, energy, and mood prior to their next injection, shortening the dosing interval to every 10 d may alleviate these symptoms. Some men prefer being treated with 75–100 mg T enanthate or cypionate im weekly in order to minimize fluctuations in serum T levels and symptoms. Administration of larger doses of T esters less frequently than every 2 wk (e.g., 300 mg im every 3 wk or 400 mg im every 4 wk) is not recommended. These higher doses usually produce very large fluctuations in blood T levels, characterized by more prolonged markedly supraphysiologic concentrations for several days following an injection and levels below the normal range after 3 wk (22). Most patients are able to learn and perform self-administration of intramuscular T ester injections or have a family member administer the injections. In men with severe, long-standing androgen deficiency, the profound alterations in sexuality, behavior, and physical appearance induced by full androgen-replacement
318 Formulation Usual adult dosage Cost a Table 1 T-Replacement Formulations Available in the United States Advantages Disadvantages Parenteral T esters T enanthate* Adult T-replacement therapy $30/mo* Long clinical experience im injections, discomfort (Delatestryl ® ) or 150–200 mg im every 2 wk (200 mg/2 wk) Inexpensive High to low T levels → T cypionate** or 75–100 mg im every wk Some dose flexibility fluctuations in libido, (Depo-Testosterone ® ) Low-dose T supplementation $15/mo** Approved for use in boys energy, mood 50–100 mg im every 2 wk (200 mg/2 wk) Erythrocytosis > with T treatment of prepubertal boys transdermal formulations 50–100 mg im monthly, increasing to every 2 wk and then to adult replacement dosages T propionate 25–50 mg im 3 times/wk $10/mo Short half-life Frequent im injections, (50 mg tiw) Rapid ↓ T levels after discomfort stopped High to low T levels → fluctuations in libido, energy, mood Rarely used Transdermal T patches Testoderm ® (matrix, 4 or 6 mg every AM $100/mo (6 mg/d) Physiological T levels, Adequate size, clean and shaven scrotal patch with circadian variation scrotum, briefs needed adhesive strips) No injections Poor adhesion to skin High DHT levels More expensive than T esters Limited dose flexibility Scrotal location unacceptable to some 318 Matsumoto
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CONTEMPORARY ENDOCRINOLOGY Androgen
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CONTEMPORARY ENDOCRINOLOGY P. Micha
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© 2003 Humana Press Inc. 999 River
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vi Preface We hope Androgens in Hea
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viii Contents 13 Androgens and Body
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x Contributors RICHARD S. LEGRO, MD
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2 Winters and Clark
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4 Winters and Clark chorionic gonad
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6 Winters and Clark LH REGULATION O
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8 Winters and Clark These enzymes a
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10 Winters and Clark -subunit mRNA
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12 Winters and Clark Fig. 3. A sche
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14 Winters and Clark Table 1 Factor
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16 Winters and Clark Table 2 Tissue
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18 Winters and Clark 11. Thomas JL,
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20 Winters and Clark 61. Dufau ML,
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22 Winters and Clark 112. Raivio T,
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24 Brown Fig. 1. Mechanism for andr
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26 Brown increase in intracellular
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28 Brown Fig. 2. Structural and fun
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30 Brown Fig. 3. Amino acid sequenc
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32 Brown tions to shuttle the AR th
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34 Brown Fig. 4. Amino acid primary
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36 Brown part of an inactive chroma
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38 Brown the external genitalia is
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40 Brown tors, as well as the trans
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42 Brown 49. Williams SP, Sigler PB
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44 Brown 100. Gregory CW, He B, Joh
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46 Plymate Table 1 Classification o
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48 Plymate In addition to the direc
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50 Plymate LABORATORY FINDINGS In p
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52 Plymate those manifesting as phe
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54 Plymate result in some improveme
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56 Plymate If both testosterone and
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58 Plymate Persistent Müllerian Du
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60 Plymate INFERTILITY RESULTING FR
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62 Plymate unaffected, contralatera
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64 Plymate SECONDARY HYPOGONADISM H
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66 Plymate Other syndromes manifest
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68 Plymate period after the burn. I
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70 Plymate These findings suggest t
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72 Plymate 49. Goebelsmann U, Horto
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74 Plymate 104. Yoshimoto Y, Moride
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76 Plymate
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78 Sutton, Amory, and Clark levels
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80 Sutton, Amory, and Clark cebo in
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82 Sutton, Amory, and Clark Finaste
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84 Sutton, Amory, and Clark through
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86 Sutton, Amory, and Clark 40. The
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88 Sutton, Amory, and Clark 88. Rob
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90 Lindzey and Korach Fig. 1. Cellu
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92 Lindzey and Korach estrogen sign
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94 Lindzey and Korach TESTIS AND DU
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96 Lindzey and Korach sufficient to
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98 Lindzey and Korach Seminal Vesic
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100 Lindzey and Korach 17. Krege JH
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102 Lindzey and Korach 68. Chang WY
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104 McPhaul on the Y chromosome det
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106 106 McPhaul
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108 McPhaul number of alleles, dele
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110 McPhaul The first mutation of t
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112 McPhaul gene. In vitro studies
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114 McPhaul risk of impaired sperma
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116 McPhaul carrying a single mutan
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118 McPhaul REFERENCES 1. Koopman P
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120 McPhaul 45. Weidemann W, Peters
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122 McPhaul 92. Koivisto P, Kononen
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124 Legro Fig. 1. The spectrum of p
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126 Legro Virilization presents wit
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128 Legro Fig. 3. The paradox of an
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130 Legro small high-density athero
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132 Legro Table 2 Syndromes or Dise
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134 Legro Insulin-Sensitizing Agent
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136 Legro is undetermined according
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138 Legro 39. Lee O, Farquhar C, To
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140 Legro
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142 Wang and Swerdloff PHARMACOLOGY
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144 Wang and Swerdloff The 17α-alk
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146 Wang and Swerdloff Table 2 Dose
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148 Wang and Swerdloff The steroid
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150 Wang and Swerdloff The inabilit
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152 Wang and Swerdloff 15. De Lorim
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154 Wang and Swerdloff
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156 Marcelli et al.
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158 Marcelli et al. Differentiated
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160 Marcelli et al. These coactivat
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162 Marcelli et al. tigators have e
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164 Marcelli et al. AR in Prostate
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166 Marcelli et al. Table 1 Androge
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168 Marcelli et al. A molecular exp
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170 Marcelli et al. The above data
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172 Marcelli et al. up to 9 yr late
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174 Marcelli et al. Three major pha
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176 Marcelli et al. vitro model of
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178 Marcelli et al. yr, survival wa
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180 Marcelli et al. 26. McKenna NJ,
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182 Marcelli et al. 78. Isaacs J, C
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184 Marcelli et al. 126. Watanabe M
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186 Marcelli et al. 177. Kousteni S
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188 Marcelli et al. 231. Colombel M
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190 Marcelli et al.
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192 Wu and von Eckardstein contrace
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194 Wu and von Eckardstein beam com
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196 Wu and von Eckardstein excess o
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198 Wu and von Eckardstein Endogeno
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Table 3 Change in Lipids in Hypogon
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Table 3 (continued) ∆LDL ∆HDL
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204 Wu and von Eckardstein THE HEMO
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206 Wu and von Eckardstein In vivo
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208 Wu and von Eckardstein (uptake
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210 Wu and von Eckardstein 4. Bhasi
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212 Wu and von Eckardstein 57. Barr
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214 Wu and von Eckardstein 107. Fra
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216 Wu and von Eckardstein 152. Zmu
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218 Wu and von Eckardstein 201. Cho
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220 Wu and von Eckardstein 250. Eic
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222 Kenny and Raisz with a cartilag
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224 Kenny and Raisz METABOLISM OF A
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226 Kenny and Raisz The level of th
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228 Kenny and Raisz REFERENCES 1. G
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230 Kenny and Raisz 51. Morishima A
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232 Kenny and Raisz 103. Snyder PJ,
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234 Basaria and Dobs losses in wome
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236 Basaria and Dobs 15 dialysis pa
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238 Basaria and Dobs duced remissio
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240 Basaria and Dobs hematocrit lev
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242 Basaria and Dobs 40. Sanchez-Me
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244 Katznelson in men with testoste
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246 Katznelson Fig. 1. Body weight,
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248 Katznelson change during treatm
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250 Katznelson testosterone or free
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252 Katznelson disproportionate dec
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254 Katznelson have been additional
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256 Katznelson 18. Marin P, Lonn L,
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258 Katznelson 71. Davis SR, McClou
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260 Bancroft Androgen Deficiency an
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262 Bancroft studies had presented
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264 Bancroft Bagatell et al. (36) g
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Page 285 and 286: 274 Bancroft 4. Studies using place
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Page 291 and 292: 280 Bancroft Women with Endocrine A
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Page 295 and 296: 284 Bancroft Men are much more awar
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Page 303 and 304: 292 Cherrier and Craft Fig. 1. Path
Page 305 and 306: 294 Cherrier and Craft ment of the
Page 307 and 308: 296 Cherrier and Craft information
Page 309 and 310: 298 Cherrier and Craft Fig. 3. Wech
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Page 317 and 318: 306 Cherrier and Craft 39. Gouchie
Page 319 and 320: 308 Cherrier and Craft 94. Kelso WM
Page 321 and 322: 310 Cherrier and Craft
Page 323 and 324: 312 Matsumoto
Page 325 and 326: 314 Matsumoto long-term benefits an
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Page 331 and 332: 320 Matsumoto Fig. 1. Mean serum T
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Page 347 and 348: 336 Richmond and Rogol PHYSIOLOGY O
Page 349 and 350: 338 Richmond and Rogol activity (28
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Page 353 and 354: 342 Richmond and Rogol curve, the h
Page 355 and 356: 344 Richmond and Rogol Permanent hy
Page 357 and 358: 346 Richmond and Rogol 46. Stanhope
Page 359 and 360: 348 Tenover In aging men, the combi
Page 361 and 362: 350 Tenover Table 1 Changes in Andr
Page 363 and 364: 352 Tenover studies in which eugona
Page 365 and 366: 354 Tenover Table 3 Testosterone Th
Page 367 and 368: 356 Tenover Table 5 ART in Older Me
Page 369 and 370: 358 Tenover be overcome with either
Page 371 and 372: 360 Tenover Laboratory tests should
Page 373 and 374: 362 Tenover 40. Kohrt WM, Malley MT
Page 375 and 376: 364 Tenover 95. Mooradian AD, Morle
Page 377 and 378: 366 Davis Table 1 Proposed Androgen
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368 Davis transdermal testosterone
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370 Davis increase in circulating t
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372 Davis (93). Most recently, Zhou
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374 Davis Table 4 Androgen Replacem
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376 Davis 8. Vierhapper H, Nowotny
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378 Davis 60. Simberg N, Titinen A,
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380 Davis
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382 Bhasin, Woodhouse, and Storer h
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384 Table 2 Effects of Testosterone
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386 Bhasin, Woodhouse, and Storer e
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388 Bhasin, Woodhouse, and Storer F
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390 Bhasin, Woodhouse, and Storer t
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Table 3 Effects of Testosterone Sup
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Table 4 Effects of Testosterone Sup
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396 Bhasin, Woodhouse, and Storer c
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398 Bhasin, Woodhouse, and Storer C
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400 Bhasin, Woodhouse, and Storer w
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402 Bhasin, Woodhouse, and Storer 4
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404 Bhasin, Woodhouse, and Storer
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406 Amory Fig. 1. The endocrinology
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408 Amory pregnancies fathered by t
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410 Amory antagonists can suppress
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412 Amory 100-mg doses of weekly TE
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414 Amory FUTURE DIRECTIONS Given t
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416 Amory 22. Oral contraception. I
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418 Amory
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420 Anawalt inadequate androgen eff
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422 Anawalt few specialty commercia
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424 Anawalt Fig. 1. (C) Secondary h
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426 Anawalt Fig. 2. Evaluation and
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428 Anawalt All men with secondary
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430 Anawalt anemia (38). With the a
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432 Anawalt osterone levels achieve
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434 Anawalt SIDE EFFECTS OF ANDROGE
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436 Anawalt 7. Rosner W. Errors in
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438 Anawalt 59. Mackey MA, Conway A
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440 Index polycystic ovaries, 131 A
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442 Index lipoid congenital adrenal
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444 Index women, 254 dihydrotestost
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446 Index Pituitary adenoma, male h
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448 Index lipoid congenital adrenal
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